Typologie d'actualités: Group Metal complexes and MRI

2022, October, 14: Seminar of Manon Isaac

Séminaire de Manon Isaac, post-doctorante dans le groupe thématique "Complexes métalliques et IRM".

Abstract:

Zinc cations play a key role as a cofactor in gene transcription and metalloenzyme functions, but also in signaling pathways in the immune system, or during fertilization. To understand its underlying function, on top of the quantification of the total amount of zinc, the detection of the labile pool and its evolution is crucial. Whatever the technique is, probes are required to visualize labile zinc. The probes have to be optimized for a given technique but also for the biological context (e.g. extracellular vs intracellular).

Manon Isaac will present several tools to detect labile zinc developed during her PhD and postdocs: design and characterization of peptidic luminescent probes, the first steps towards a device to detect zinc released by the egg after in vitro fertilization, and MRI zinc probes.

 

4th scientific days of the GDR AIM

The 4th scientific days of the GDR AIM (gdraim.cnrs-orleans.fr) organized jointly with the RE1 of France Life Imaging will take place from October 03 to 05, 2022 in Orléans.

The program will take place over four half-days, from Monday October 3rd at 12:00 p.m. to Wednesday October 5th at 1:30 p.m.

With 90 registered participants and a rich program, these days will be a fine representation of French research in the chemistry of imaging probes.

We will also have the pleasure of welcoming 4 foreign speakers:

  • Kristina Djanashvili (Delft University of Technology, The Netherlands)
  • Christophe Portal (Edinburgh Molecular Imaging Ltd)
  • Gyula Tircso (Univ. of Debrecen, Hungary)
  • Carlos Platas (Univ. of Coruna, Spain)

See the programm

Eva Jakab Toth receives the “Torsten Almén” Award

Eva Jakab Toth, co-leader of the "Metal complexes and MRI" group, received the "Torsten Almén" Award for her pioneering research on contrast agents, from the "Contrast Media Research" committee of the World Molecular Imaging Society (WMIS).

This biannual prize rewards unique research activities that have shaped the field of contrast agents. Torsten Almén was a pioneer in the field of non-ionic contrast agents for radiography. His work forever revolutionized the research and clinical use of X-ray imaging agents. In the same spirit, the committee specifically identified "the creativity of the preclinical and translational work of Eva Jakab Toth, in the design, deep characterization and application of paramagnetic MRI contrast agents".

Eva Jakab Toth gave the “Torsten Almén Medal Award” lecture at the 2022 « Contrast Media Research » Symposium in Annapolis, Maryland (August 21-25, 2022).

 

In Cellulo and In Vivo Comparison of 3 helper lipids for Lipid Nanoparticle Formulation of mRNA

LNPs are a leading class of mRNA delivery systems. LNPs are made of an ionizable lipid, a polyethyleneglycol (PEG)-lipid conjugate and helper lipids. The success of LNPs is due to proprietary ionizable lipids and appropriate helper lipids.

Using a benchmark lipid (D-Lin-MC3) researchers compared the ability of three helper lipids to transfect dendritic cells in cellulo and in vivo. Studies revealed that the choice of helper lipid does not influence the transfection efficiency of immortalized cells but, LNPs prepared with DOPE (dioleylphosphatidylethanolamine) and β-sitosterol were more efficient for mRNA transfection in murine dendritic cells than LNPs containing DSPC (distearoylphosphatidylcholine).

This higher potency of DOPE and β-sitosterol LNPs for mRNA expression was also evident in vivo but only at low mRNA doses.

References of the article published in Nanomaterials:
Ayoub Medjmedj, Albert Ngalle-Loth, Rudy Clemnçon, Josef Hamacek, Chantal Pichon and Federico Perche
In Cellulo and In Vivo Comparison of Cholesterol, Beta-Sitosterol and Dioleylphosphatidylethanolamine for Lipid Nanoparticle Formulation of mRNA
Nanomaterials 2022, 12(14), 2446; https://doi.org/10.3390/nano12142446

Mariano Gago prize awarded to the collaboration between the group of Eva Jakab Toth and the University of Coimbra, Portugal

2022 is the year of the France-Portugal cooperation, organized by the French and Portuguese Ministries for Europe, Foreign Affairs and Culture.

This “France-Portugal 2022” season is an opportunity to highlight many events marking the cooperation between the two countries, including several in the field of Higher Education and Research.

In this context, the Ministry of Higher Education, Research and Innovation and the Academy of Sciences are pleased to propose a scientific prize which distinguishes existing cooperation between French and Portuguese teams, and to offer them an opportunity to deepen the cooperation in the years to come. The four prizes awarded in 2022 cover all scientific disciplines.

In this frame, the collaboration carried out for many years by Eva Jakab Toth with the University of Coimbra has been rewarded with the Mariano Gago Prize. This collaboration concerns the development of imaging agents based on metalloporphyrins for the detection of tissue redox states.

The official award ceremony helded at the Academy of Sciences on Tuesday, June 21, 2022.

The first molecules which really prefer manganese(II) over zinc(II)

Manganese(II) complexes meet increasing interest in biomedical applications, in particular as potential Magnetic Resonance Imaging contrast agents with a better biocompatibility and safety profile than the currently used gadolinium(III) chelates. However, we severely lack chelating ligands that enable high MnII complex stability and especially good selectivity for manganese(II) versus zinc(II), the most relevant biological competitor. In an article published in Angewandte Chemie Int. Ed., the “Metal complexes and MRI” group in collaboration with the group of Peter Comba at the University of Heidelberg, has identified novel cage molecules which, for the first time, satisfy these criteria. The bispidine derivative ligands provide rigid and large coordination cavities that perfectly match the slightly larger size of MnII, yielding eight-coordinate MnII complexes with record stabilities. In contrast, the smaller ZnII ion cannot accommodate all ligand donors, resulting in highly strained and less stable six-coordinate complexes.

Combined theoretical and experimental data demonstrate unprecedented selectivity, with up to 10 orders of magnitude higher stability for the manganese(II) than for the zinc(II) analogues, in sharp contrast to usual coordination chemistry rules.

 

https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202115580